Objective:To optimize the animal model of liver injury that can properly represent the pathological characteristics of dampness-heat jaundice syndrome of traditional Chinese medicine.Methods:The liver injury in the mo...Objective:To optimize the animal model of liver injury that can properly represent the pathological characteristics of dampness-heat jaundice syndrome of traditional Chinese medicine.Methods:The liver injury in the model rat was induced byα-naphthylisothiocyanate(ANIT) and carbon tetrachloride(CCl_4) respectively,and the effects of Yinchenhao Decoction(茵陈蒿汤,YCHD),a proved effective Chinese medical formula for treating the dampness-heat jaundice syndrome in clinic,on the two liver injury models were evaluate...展开更多
目的探讨α-异硫氰酸萘酯(ANIT)致胆汁淤积性肝炎的机制。方法 60只成年健康雄性SD大鼠,随机分为正常对照组(N组,30只)和模型组(ANIT组,30只),按灌胃后不同时相再分为24、48、72 h 3个亚组,每个亚组各10只。检测血清中ALT、AST、GGT和T...目的探讨α-异硫氰酸萘酯(ANIT)致胆汁淤积性肝炎的机制。方法 60只成年健康雄性SD大鼠,随机分为正常对照组(N组,30只)和模型组(ANIT组,30只),按灌胃后不同时相再分为24、48、72 h 3个亚组,每个亚组各10只。检测血清中ALT、AST、GGT和TBil的水平;检测肝组织中丙二醛(MDA)的水平;光镜观察肝组织病理学改变;透射电镜观察胆小管超微结构的改变;共聚焦激光扫描显微镜分析异硫氰酸荧光素标记的鬼笔环肽的平均荧光强度,间接确定纤维形肌动蛋白(F-actin)水平的变化。计量资料组间比较采用t检验。结果大鼠在灌服ANIT后,血清ALT、AST、GGT和TBil的水平和肝组织中MDA的水平较对照组显著增加;肝小叶结构破坏,肝细胞有透明变性,可见点状、片状、灶状坏死区及中性粒细胞浸润,多局限于胆管周围的肝细胞,胆管上皮和纤维组织增生,窦周间隙增宽,胆小管扩张,微绒毛大量脱落,管腔内有微胆栓形成;F-actin的荧光染色明显紊乱、强度减弱。上述变化48 h最明显,72 h开始恢复,但与N组相比,差异均有统计学意义(P值均<0.05)。结论 ANIT可引起肝组织发生脂质过氧化损伤,导致肝细胞变性坏死,胆小管微绒毛破坏,微胆栓形成以及胆小管F-actin的表达下降,从而影响肝脏对胆汁的排泄功能,引起胆汁淤积性肝炎。展开更多
Objective To explore the molecular mechanisms of the total flavonoids extracted from the flowers of Abelmoschus manihot（TFA） against α-naphthylisothiocyanate（ANIT）-induced cholestasis. Methods The hepatoprotectiv...Objective To explore the molecular mechanisms of the total flavonoids extracted from the flowers of Abelmoschus manihot（TFA） against α-naphthylisothiocyanate（ANIT）-induced cholestasis. Methods The hepatoprotective activities of TFA（125, 250 and 500 mg/kg） were investigated on ANIT-induced cholestatic liver injury in rats. Serum levels of alanine aminotransferase（ALT）, aspartate aminotransferase（AST）, total bilirubin（TBIL）, total bile acid（TBA）, and bile flow were measured to evaluate the protective effect of TFA. Furthermore, the hepatic m RNA and protein levels of transports, multidrug resistance-associated protein 2（MRP2）, bile salt export pump（BSEP）, and Na＋-taurocholate cotransporting polypeptide（NTCP） were investigated to elucidate the protective mechanisms of TFA against ANIT-induced cholestasis. Results Pretreatment of TFA significantly and dose-dependently decreased the ANIT-induced elevation of serum ALT, AST, TBIL, and TBA levels and increased the ANIT-induced suppression of bile flow. Moreover, TFA was found to increase the expression of liver MRP2, BSEP, and NTCP in both protein and m RNA levels in ANIT-induced liver injury in rats with cholestasis. Conclusion TFA exerts a therapeutic effect on ANIT-induced liver injury in rats with cholestasis, possibly through regulating the expressions of hepatic transporters.展开更多
Objective To investigate the hepatoprotective effects of Paeoniae Radix Rubra(PRR)at different doses against α-naphthylisothiocyanate(α-NIT)-induced acute cholestatic hepatitis in rats.Methods Rats were ig admini-st...Objective To investigate the hepatoprotective effects of Paeoniae Radix Rubra(PRR)at different doses against α-naphthylisothiocyanate(α-NIT)-induced acute cholestatic hepatitis in rats.Methods Rats were ig admini-strated with vehicle or PRR[(1,9,18,36,54,72,and 81 g/(kg·d)]3 d before and 2 d afterα-NIT(60 mg/kg)ig administration.The general status of rats,histopathology of liver,serum alanine aminotransaminase,aspartate aminotransaminase,total bilirubin,direct bilirubin,and alkaline phosphatase levels,were observed at respective time points(24 and 48 h)afterα-NIT administration.Using cluster analysis and correspondence analysis,the 'dose-effect-response'relationships of PRR were evaluated.Results The results showed that compared with model group,the serum biochemistry index significantly decreased with the increasing of PRR dosage(P<0.01), and the change and necrosis of hepatic cellula,and inflammatory cell infiltration were gradually alleviated. However,the improvement was not obviously found in the low-dose group[1 g/(kg·d)].The cluster analysis and correspondence analysis results showed that different doses of PRR could significantly ameliorateα-NIT-induced acute cholestatic hepatitis of rats in a dose-dependent manner.Conclusion The experiments show that administration doses of PRR in clinical use should be added properly in order to gain the expectant therapeutic effect,especially in the treatment of heavy acute cholestasis hepatitis.展开更多
基金Supported by the Major State Basic Research Development Program of China(973 Program,No.2005CB523406)
文摘Objective:To optimize the animal model of liver injury that can properly represent the pathological characteristics of dampness-heat jaundice syndrome of traditional Chinese medicine.Methods:The liver injury in the model rat was induced byα-naphthylisothiocyanate(ANIT) and carbon tetrachloride(CCl_4) respectively,and the effects of Yinchenhao Decoction(茵陈蒿汤,YCHD),a proved effective Chinese medical formula for treating the dampness-heat jaundice syndrome in clinic,on the two liver injury models were evaluate...
基金National Nature Science Foundation of China(No.30572350)New Drug Foundation of State Administration of Traditional Chinese Medicine(DIX005A)
文摘Objective To explore the molecular mechanisms of the total flavonoids extracted from the flowers of Abelmoschus manihot（TFA） against α-naphthylisothiocyanate（ANIT）-induced cholestasis. Methods The hepatoprotective activities of TFA（125, 250 and 500 mg/kg） were investigated on ANIT-induced cholestatic liver injury in rats. Serum levels of alanine aminotransferase（ALT）, aspartate aminotransferase（AST）, total bilirubin（TBIL）, total bile acid（TBA）, and bile flow were measured to evaluate the protective effect of TFA. Furthermore, the hepatic m RNA and protein levels of transports, multidrug resistance-associated protein 2（MRP2）, bile salt export pump（BSEP）, and Na＋-taurocholate cotransporting polypeptide（NTCP） were investigated to elucidate the protective mechanisms of TFA against ANIT-induced cholestasis. Results Pretreatment of TFA significantly and dose-dependently decreased the ANIT-induced elevation of serum ALT, AST, TBIL, and TBA levels and increased the ANIT-induced suppression of bile flow. Moreover, TFA was found to increase the expression of liver MRP2, BSEP, and NTCP in both protein and m RNA levels in ANIT-induced liver injury in rats with cholestasis. Conclusion TFA exerts a therapeutic effect on ANIT-induced liver injury in rats with cholestasis, possibly through regulating the expressions of hepatic transporters.
基金National Basic Research Program of China(2007CB512607)
文摘Objective To investigate the hepatoprotective effects of Paeoniae Radix Rubra(PRR)at different doses against α-naphthylisothiocyanate(α-NIT)-induced acute cholestatic hepatitis in rats.Methods Rats were ig admini-strated with vehicle or PRR[(1,9,18,36,54,72,and 81 g/(kg·d)]3 d before and 2 d afterα-NIT(60 mg/kg)ig administration.The general status of rats,histopathology of liver,serum alanine aminotransaminase,aspartate aminotransaminase,total bilirubin,direct bilirubin,and alkaline phosphatase levels,were observed at respective time points(24 and 48 h)afterα-NIT administration.Using cluster analysis and correspondence analysis,the 'dose-effect-response'relationships of PRR were evaluated.Results The results showed that compared with model group,the serum biochemistry index significantly decreased with the increasing of PRR dosage(P<0.01), and the change and necrosis of hepatic cellula,and inflammatory cell infiltration were gradually alleviated. However,the improvement was not obviously found in the low-dose group[1 g/(kg·d)].The cluster analysis and correspondence analysis results showed that different doses of PRR could significantly ameliorateα-NIT-induced acute cholestatic hepatitis of rats in a dose-dependent manner.Conclusion The experiments show that administration doses of PRR in clinical use should be added properly in order to gain the expectant therapeutic effect,especially in the treatment of heavy acute cholestasis hepatitis.
